Cerebrovascular disease and strokes are a major cause of morbidity and mortality throughout the world. Strokes may develop as a complication of hypertension or other cardiovascular disorders, or may be caused by diseases of parenchymal brain blood vessels and disturbances in local cerebral blood flow. The neurotransmitters serotonin and norepnephrine have been detected in the walls of cerebral blood vessels where they have been implicated in the regulation if intraparenchymal blood flow. Both substances are vasoactive and cause blood vessels to contract when applied directly. This proposal requests support to develop a program of research that will explore the biochemistry and pharmacology of vascular neurotransmitters within brain intraparenchymal blood vessels. Studies have utilized a recently perfected method for separating blood vessels from surrounding neuropil and will extend our studies on the control of serotonin levels within this brain fraction. Related studies will characterize the levels of other neurotransmitters and their biosynthetic and degradative enzymes within isolated microvessels and will attempt to idetify the loci of origin of the neurons that project onto these blood vessels. Pharmacological and morphological techniques are also being utilized. The proposed research may provide useful information about neurotransmission mechanisms regulation brain vascular tissue which may, in turn, underlie new strategies for the prophylaxis and treatment of carebrovascular-disease.